Fresh, Frozen or Lyophilized Fecal Microbiota Transplantation for Multiple Recurrent C. Difficile Associated Diarrhea

The following safety endpoints will be evaluated in this study.

Medical conditions

Clinical improvement is monitored by telephone/email and or E-mail during 90 days after FMT.
Minor clinical management of the subject with over the counter medication (e.g. loperamide,
acetaminophen and Saccharomyces boulardii [probiotic]) will be performed in the case of mild
diarrhea and abdominal pain.

All subjects will be followed up by phone the day after FMT to assess health status during
week one. Study subjects will be monitored on approximately days 7, 14 and 30 after FMT, at
which time we will review the recipient diary with the recipient to review any adverse
experience or medication taken since the medical history obtained at FMT.

Investigators should determine if any adverse experience or medication need to be further
studied. Donor will be contacted and tested if it is necessary. All actions will be recorded
on with medical condition, dates of adverse experience and medication taken, indication for
new medication taken, and total daily dose (Patient Data Collection Form).

Recipients should be instructed at FMT to contact the Investigator if they have any
questions regarding adverse experience or the appropriateness of a medication after FMT.

Monitoring for safety

The following definitions of terms are guided by the International Conference of
Harmonization and US Code of Federal Regulations (21 CFR 312.32).

An adverse experience is any unfavorable or unintended sign, symptom, of disease temporally
associated with FMT procedure, whether or not considered related to the procedure,
including, but not limited to:

- Any symptom not previously reported by the recipients (Recent Medical History)

- An exacerbation of a pre-existing illness, increases in the frequency and/or severity
of the signs or symptoms of CDAD (defined as positive C. difficile toxin test and
enteric symptoms)

- A significant increase in frequency or intensity of a pre-existing episodic event or
condition

- A condition first detected or diagnosed after study drug administration even through
the condition may have been present before the procedure

Details of all adverse experiences that occur after FMT through approximately day 90 visit
will be collected as indicated above.

Serious adverse experience is any adverse experience that:

- Results in death

- Is life threatening (at immediate risk of death from the procedure as it occurred)

- Requires inpatient hospitalization (overnight stay) or prolongs a current
hospitalization

- Causes a persistent or significant disability/incapacity

- Medical important (any event that requires medical or surgical intervention to prevent
one of the outcomes listed above)

The investigator will exercise medical and scientific judgment when deciding whether
expeditious reporting is appropriate in other situations not strictly meeting the listed
criteria above. The investigators will meet/discuss with experts in the field if there is a
question of whether the adverse experience would be considered serious.

Severity - The adverse experience will be documented on the appropriate page in the Patient
Diary according to the following descriptors:

- Mild: associated with no limitation of usual activities or only slight discomfort

- Moderate: associated with limitation of usual activities or significant discomfort

- Severe: associated with inability to carry out usual activities or very marked
discomfort

Relationship - the relationship of adverse experience to FMT will be assigned by the
Investigator according to the following definitions:

- Probable: a reaction that follows a reasonable temporal sequence from the procedure
that follows a known or expected response pattern to the suspected procedure and that
could not be reasonably explained by the known characteristics of that patient's
clinical state

- Possible: a reaction that follows a reasonable temporal sequence from the procedure
that follows a known or expected response pattern to the procedure but could readily
have been produced by a number of other factors

- Unlikely: a reaction that does not follow a reasonable temporal sequence from the
procedure but for which causality from FMT cannot be ruled out.

- Not related: a reaction for which sufficient data exist to indicate that the etiology
is unrelated to the procedure

Pre-existing signs and symptoms and medical conditions

Medical conditions that are present at or before the procedure that manifest with the same
severity or frequency will not be recorded as adverse experience. Similarly, signs or
symptoms related to a pre-existing disease will not be recorded as adverse experience unless
there is an increase in the severity or frequency of the signs or symptoms. These
pre-existing conditions, signs, or symptoms will be recorded on the Recent Medical History
Form.

Progression of underlying conditions as an adverse experience

If the progression of the underlying condition might be reasonably anticipated given the
nature and severity of the underlying condition, then the progression of the underlying
condition per se will not constitute an adverse experience. However, if the progression of
the underlying condition is fatal, then the progression of the underlying condition should
be reported as an adverse experience.

Recording and documenting adverse experience

The Investigator must completely and promptly record each new adverse experience and serious
adverse experience, even if the relationship of adverse experience to the procedure is
assessed by the Investigator to be "unlikely" or "not related". In addition, the
investigator must document and follow serious adverse experiences that occur from the
procedure through 90 days after the FMT. The Investigator should attempt, if possible, to
establish a diagnosis based on the presenting signs and symptoms. If an adverse experience
meets the definition of a serious adverse experience then the Investigator must also
complete the serious adverse experience, and also send any supporting source documents
directly to the University of Texas Health Science Center IRB as soon as the event is
discovered. At each visit, after the patient has had an opportunity to mention any problems
spontaneously, the Investigator (or designee) will inquire about adverse experience by
asking the standard questions listed in, such as:

- Have you had any medical problems since your last visit?

- Have any medical problems present at your last visit changed, i.e., stopped, worsened,
or improved?

- Have you taken any new medicines, other than study drug, since your last visit?

Any spontaneous adverse experience information provided by the patient will be reported. If
an adverse experience has not resolved at the time of the Final Visit, the Investigator
should evaluate the status of the adverse experience at the Follow-Up telephone/email
contact (day 60) and update to reflect the status of the adverse experience (e.g. ongoing or
resolved).

Investigator reporting of serious adverse experience

All serious adverse experience must be reported to the University of Texas Health Science
IRB using the serious adverse experience facsimile or email or by telephone/email as soon as
the serious adverse experience is discovered, and within 24 hours after the Investigator
recognizes or classifies the event as a serious adverse experience. A brief description of
the event must be provided at the time of the initial serious adverse experience report. The
initial serious adverse experience report should be followed up by additional information
using the serious adverse experience within 48 hours. The reports should identify the
patient by their unique patient number instead of names. The completed serious adverse
experience Form will be used by the investigators in regulatory filings. The investigator is
responsible for continuing to report to the University of Texas Health Science IRB any new
or relevant follow-up information obtained concerning the serious adverse experience. The
results of any additional assessments conducted must be also reported to the University of
Texas Health Science IRB.

Notification of post-study serious adverse experience

Investigators are not obligated to actively seek follow-up information for patients with
adverse experience after the conclusion of the study (i.e., > 90 days after the FMT
procedure). However, if the investigator becomes aware of an adverse experience that occurs
after the patient completes and the adverse experience is considered by the Investigator to
be at least possibly related to study procedure, the investigator must notify the University
of Texas Health Science Center IRB.

Inclusion Criteria:

Recipients

1. Male and female patients ≥ 18 years of age

2. Sexually active male and female patients of child-bearing potential must agree to use
an effective method of birth control during the treatment and follow-up period

3. Female patients of child-bearing potential must have a negative pregnancy test in the
72 hours before the procedure

4. Required to sign an informed consent form

5. Deemed likely to survive for ≥ 3 months after enrolment

6. Diagnosis of ≥ 3 recurrent CDAD (RCDAD) bouts in outpatients or ≥ 2 bouts of CDAD in
an inpatient without other explanation for diarrhea and with ≥ 2 positive fecal tests
for C. difficile toxin

7. Referred by subjects attending physician who will provide non-transplant care for the
subject and follow up at 1, 7, 14, 30 days after FMT

8. Received at least one course of adequate antibiotic therapy for CDAD (≥ 10 days of
vancomycin at a dose of ≥125 mg four times per day, ≥ 10 days of metronidazole at a
dose of 500mg three times per day or fidaxomixin 200mg twice a day for 10 days

9. Anti-CDI antibiotic treatment stopped 2-4 days before the transplantation

Donors

1. Able to provide and sign informed consent

2. Able to complete and sign the donor questionnaire

3. Able to adhere to fecal transplantation stool collection requirements

Exclusion Criteria:

Recipients

1. Patients with neutropenia with absolute neutrophil count <0.5 x 109/L

2. Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray

3. Peripheral white blood cell count > 15.0 x 109/L AND temperature > 38.0 °C

4. Active gastroenteritis due to Salmonella, Shigella, E. coli 0157:H7, Yersinia or
Campylobacter, and Norovirus

5. Presence of colostomy

6. Unable to tolerate HBT for any reason

7. Requiring systemic antibiotic therapy for more than 7 days

8. Actively taking Saccharomyces boulardii or other probiotic

9. Severe underlying disease such that the patient is not expected to survive for one or
more years or unstable medical condition requiring daily change in treatments

10. Prolonged compromised immunity due to cytotoxic chemotherapy or HIV infection

Donors

1. Test positive for any of variables

2. History of any type of active cancer or autoimmune disease

3. History of risk factors for acquisition of HIV, syphilis, Hepatitis B, Hepatitis C,
prion or any neurological disease as determined by the donor questionnaire

4. History of gastrointestinal disorder, e.g., inflammatory bowel disease, irritable
bowel syndrome, chronic constipation or diarrhea

5. Antibiotic use or any systemic immunosuppressive agents in the 3 months prior to
stool donation

6. Receipt of any type of live vaccine within 3 months prior to stool donation

7. Current or previous medical or psychosocial condition

8. Body mass index over 30